DESCRIPTION (Applicant's Description): The pharynx of the nematode Caenorhabditis elegans is a distinct organ consisting of five different cell types, including muscles, neurons, epithelial cells, secretory glands cells and structural cells termed marginal cells. We are interested in how these cells are produced during embryogenesis, and how they are assembled into a functional organ. To address these questions we are focusing on understanding the mechanisms controlling gene expression in one of these cell types, the pharyngeal muscles. While nematodes do not have hearts, the pharyngeal muscles share a number of functional and developmental similarities with cardiac muscle in other species, including humans. We therefore believe that insights gained from this work may have a direct bearing on our understanding cardiac development and function. Pharyngeal muscle gene expression is regulated by a combination of cell type- and organ-specific signals. Factors involved in organ-specific regulation include the winged-helix factor PHA-4 and a novel protein PEB-1, which are both expressed broadly in many pharyngeal cell types. Factors involved in cell type-specific regulation include the homeodomain factor CEH-22 and the basic leucine zipper-related factor ZIP-1, which are expressed more specifically in the pharyngeal muscles. We hypothesize these factors cooperate to regulate pharyngeal muscle development and gene expression. CEH-22 is the earliest known marker of pharyngeal muscle differentiation, and we are currently examining how ceh-22 gene expression is regulated to identify the very early steps specifying pharyngeal muscle fate. We are also investigating how these factors interact with each other to regulate gene expression, and whether these interactions may be conserved in vertebrate heart development. Finally we are specifically examining role the PEB-l plays during pharyngeal development by isolating and characterizing apeb-1 mutant.